Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation

Abstract

, § and the Acute Liver Failure Study GroupBromfenac, a nonnarcotic analgesic nonsteroidal anti-inflammatory drug, was associated with reversible, minor elevations in serum aminotransferase levels during clinical trials. The aim of this study is to describe the clinical, laboratory, and histological features of 4 patients with severe bromfenac hepatotoxicity identified at 3 tertiary care centers participating in the US Acute Liver Failure Study Group. Bromfenac was administered for chronic musculoskeletal disorders to 4 women in therapeutic doses of 25 to 100 mg/d for a minimum of 90 days. All patients reported a prodrome of malaise and fatigue and presented with severe, symptomatic hepatocellular injury with associated hypoprothrombinemia. None of the subjects had underlying liver or kidney disease, and there was no evidence of a hypersensitivity reaction. Other identifiable causes of acute liver failure were uniformly excluded. Despite supportive measures, all the subjects developed progressive liver failure over 5 to 37 days, leading to emergency liver transplantation in 3 patients and death in 1 patient while awaiting transplantation. Extensive confluent parenchymal necrosis that appeared to begin in the central zones and was accompanied by a predominantly lymphocytic infiltrate was noted in all the livers examined. Nodular regeneration was seen in the 2 patients with a more protracted clinical course. Administration of therapeutic doses of bromfenac for greater than 90 days was associated with the development of acute liver failure leading to liver transplantation or death in 4 adult women. The poor outcomes observed in this series, coupled with the inability to identify individuals at risk for severe, idiosyncratic bromfenac hepatotoxicity, preclude further use of bromfenac in the medical community.

Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium

“…Nonetheless, these findings raise some important questions that warrant further investigation. Although no systemic adverse effects have been associated with the ophthalmic use of bromfenac sodium to date, it has only recently been made available for ophthalmic use and rare cases of idiosyncratic hepatotoxicity have been associated with the long-term use of oral bromfenac [36][37][38][39] . Idiosyncratic hepatotoxicity is an unpredictable, immune-mediated response that is not dose-dependent.…”

Etiologies of acute liver failure

“…The second most common class of drugs implicated is the nonsteroidal anti-inflammatory drugs [24 ] including several that have been removed from the market such as bromfenac [25]. An epidemiologic study conducted in Spain and France found disparate incidences in the two countries that could possibly be explained by different patterns of drug use or by variation in the data collection techniques [26].…”

ACG Clinical Guideline: The Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury

“…Despite these efforts, the manufacturer and the FDA continued to receive reports of severe injuries, including reports of death or need for liver transplantation (Moses and Schroeder et al 1999;Hunter and Johnston et al 1999;Rabkin and Smith et al 1999;Fontana and McCashland et al 1999). Given the availability of other effective NSAIDs, bromfenac was withdrawn from the market in June 1998.…”